Self-sealing PTFE vascular graft and manufacturing methods

ABSTRACT

An implantable microporous ePTFE tubular vascular graft exhibits long term patency, superior radial tensile strength and suture hole elongation resistance. The graft includes a first ePTFE tube and a second ePTFE tube circumferentially disposed over the first tube. The first ePTFE tube exhibits a porosity sufficient to promote cell endothelization, tissue ingrowth and healing. The second ePTFE tube exhibits enhanced radial strength in excess of the radial tensile strength of the first tube.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.10/822,200, filed Apr. 9, 2004, now allowed, which is a continuation ofU.S. application Ser. No. 10/212,609, filed on Aug. 5, 2002, now U.S.Pat. No. 6,719,783, which is a continuation of U.S. application Ser. No.09/525,710, filed on Mar. 14, 2000, now U.S. Pat. No. 6,428,571, whichis a continuation-in-part of U.S. application Ser. No. 09/008,265, filedon Jan. 16, 1998, now U.S. Pat. No. 6,036,724, which is a divisional ofU.S. application Ser. No. 08/588,052, filed on Jan. 22, 1996, now U.S.Pat. No. 5,800,512, the full contents of all of which are incorporatedherein by reference.

FIELD OF INVENTION

The present invention relates generally to a tubular implantableprosthesis such as vascular grafts and endoprostheses formed of porouspolytetrafluoroethylene. More particularly, the present inventionrelates to a multi-layered tubular self-sealing graft or endoprosthesisformed from primarily expanded polytetrafluoroethylene.

BACKGROUND OF THE INVENTION

It is well known to use extruded tubes of polytetrafluoroethylene (PTFE)as implantable intraluminal prostheses, particularly vascular grafts.PTFE is particularly suitable as an implantable prosthesis as itexhibits superior biocompatability. PTFE tubes may be used as vasculargrafts in the replacement or repair of a blood vessel as PTFE exhibitslow thrombogenicity. In vascular applications, the grafts aremanufactured from expanded polytetrafluoroethylene (ePTFE) tubes. Thesetubes have a microporous structure which allows natural tissue ingrowthand cell endothelization once implanted in the vascular system. Thiscontributes to long term healing and patency of the graft.

Grafts formed of ePTFE have a fibrous state which is defined byinterspaced nodes interconnected by elongated fibrils. The spacesbetween the node surfaces that is spanned by the fibrils is defined asthe intemodal distance (IND). A graft having a large IND enhances tissueingrowth and cell endothelization as the graft is inherently moreporous.

The art is replete with examples of microporous ePTFE tubes useful asvascular grafts. The porosity of an ePTFE vascular graft can becontrolled by controlling the IND of the microporous structure of thetube. An increase in the IND within a given structure results inenhanced tissue ingrowth as well as cell endothelization along the innersurface thereof. However, such increase in the porosity of the tubularstructure also results in reducing the overall radial tensile strengthof the tube as well as reducing the ability for the graft to retain asuture placed therein during implantation. Also, such microporoustubular structures tend to exhibit low axial tear strength, so that asmall tear or nick will tend to propagate along the length of the tube.

The art has seen attempts to increase the radial tensile and axial tearstrength of microporous ePTFE tubes. These attempts seek to modify thestructure of the extruded PTFE tubing during formation so that theresulting expanded tube has non-longitudinally aligned fibrils, therebyincreasing both radial tensile strength as well as axial tear strength.U.S. Pat. No. 4,743,480 shows one attempt to reorient the fibrils of aresultant PTFE tube by modifying the extrusion process of the PTFE tube.

Other attempts to increase the radial tensile, as well as axial tearstrength of a microporous ePTFE tube include forming the tubular graftof multiple layers placed over one another. Examples of multi-layeredePTFE tubular structures useful as implantable prostheses are shown inU.S. Pat. Nos. 4,816,338; 4,478,898 and 5,001,276. Other examples ofmulti-layered structures are shown in Japanese Patent Publication Nos.6-343,688 and 0-022,792.

Artificial bypass grafts are often used to divert blood flow arounddamaged regions to restore blood flow. Vascular prostheses may also beused for creating a bypass shunt between an artery and vein. Thesebypass shunts are often used for multiple needle access, such as isrequired for hemodialysis treatments. These artificial shunts arepreferable to using the body's veins, mainly because veins may eithercollapse along a puncture track or become aneurysmal, leaky or clotted,causing significant risk of pulmonary embolization.

While it is known to use ePTFE as a vascular prosthesis, and thesevascular prostheses have been used for many years for vascular accessduring hemodialysis, there remain several problems with theseimplantable ePTFE vascular access grafts. One major drawback in usingePTFE vascular grafts as access shunts for hemodialysis is that becauseof ePTFE's node-fibril structure, it is difficult to elicit naturalocclusion of suture holes in the vascular prosthesis made from ePTFEtubing. As a result, blood cannot typically be withdrawn from an ePTFEvascular graft until the graft has become assimilated with fibrotictissue. This generally takes 2 to 3 weeks after surgery. Furthermore,ePTFE's propensity for axial tears make it undesirable as a vascularaccess graft, as punctures, tears, and other attempts to access theblood stream may cause tears which propagate axially with the grain ofthe node fibril structure.

Providing a suitable vascular access graft has also been attempted inthe prior art. Schanzer in U.S. Pat. No. 4,619,641 describes a two-piececoaxial double lumen arteriovenous graft. The Schanzer graft consists ofan outer tube positioned over an inner tube, the space between beingfilled with a self-sealing adhesive. The configuration of this coaxialtube greatly increases the girth of the graft, and limits theflexibility of the lumen which conducts blood flow. Herweck et al., inU.S. Pat. No. 5,192,310 describes a self-sealing vascular graft ofunitary construction comprising a primary lumen for blood flow, and asecondary lumen sharing a common sidewall with the primary lumen. Anon-biodegradable self-sealing elastomeric material is disposed betweenthe primary and secondary lumen.

While each of the above-referenced patents disclose self-sealingvascular grafts, none disclose a tubular access graft structureexhibiting enhanced radial tensile strength, as well as enhancedresistance to axial tear strength. Furthermore, the multi-layered ePTFEtubular structures and vascular access grafts of the prior art exhibitsmaller microporous structure overall, and accordingly a reduction inability of the graft to promote endothelization along the inner surface.Furthermore, Schanzer does not provide a self-sustaining resealablelayer, but rather an elastomeric layer which “fills” the area betweenthe two tubes.

It is therefore desirable to provide a self-sealing ePTFE graft for usein a human body which exhibits increased porosity especially at theinner surface thereof while retaining a high degree of radial strengthat the external surface thereof. The graft may preferably be used as avascular access graft.

It is further desirous to produce an ePTFE vascular access graft whichexhibits increased porosity at the outer surface thereof while retaininga high degree of radial tensile and suture retention strengths.

It is still further desirous to provide a self-sealing graft withincreased resistance to axially propagating tears.

SUMMARY OF THE INVENTION

It is an advantage of the present invention to provide a self-sealingePTFE graft with increased resistance to axially propagating tears.

It is a further advantage of the present invention to provide aself-sealing ePTFE graft providing superior assimilation capabilitiesand resealable properties.

It is a further advantage of the present invention to provide aself-sealing ePTFE vascular graft exhibiting an enhanced microporousstructure while retaining superior radial strength.

It is a still further advantage of the present invention to provide anePTFE tubular structure having an inner portion exhibiting enhancedporosity and an outer portion exhibiting enhanced radial tensilestrength, suture retention, and suture-hole elongation characteristics.

It is yet another advantage of the present invention to provide amulti-layered ePTFE tubular vascular graft having an inner layer whichhas a porosity sufficient to promote cell endothelization and an outerlayer having a high degree of radial tensile strength.

It is an additional advantage of the present invention to provide amulti-layered ePTFE tubular vascular access graft having an outer layerwhose porosity is sufficient to promote enhanced cell growth and tissueincorporation, hence more rapid healing, and an inner layer having ahigh degree of strength.

In the efficient attainment of these and other advantages, the presentinvention provides a self-sealing ePTFE graft comprising a firstexpanded polytetrafluoroethylene (ePTFE) tubular structure having afirst porosity, a second ePTFE tubular structure having a secondporosity less than said first porosity, said second ePTFE tubularstructure being disposed externally about said first ePTFE tubularstructure to define a distinct porosity change between said first andsecond tubular structures, and a resealable polymer layer interposedbetween said first and second ePTFE tubular structures.

In another embodiment, the present invention provides an ePTFEself-sealing graft, the graft formed of a first EPTFE tubular structure,a second ePTFE tubular structure disposed externally about said firstEPTFE tubular structure, and further including a self-sustainedresealable polymer layer interposed between the first and second ePTFEtubular structures.

The ePTFE self-sealing graft preferably may be used as a vascular accessgraft. As more particularly described by way of the preferred embodimentherein, the first and second ePTFE tubular structures are formed ofexpanded polytetrafluoroethylene (ePTFE). Further, the second ePTFEtubular structure is adheringly supported over the first ePTFE tubularstructure to form a composite tubular graft. The strength of thisadhesion can be varied as desired to control the characteristicsexhibited by the resultant composite structure.

In its method aspect, the present invention provides a method of forminga self-sealing ePTFE graft. The method includes the steps of providing afirst ePTFE tubular structure having a desired porosity and strengthcombination. A second ePTFE tubular structure is provided, also havingthe desired porosity and strength combination. The second ePTFEstructure is disposed over the first ePTFE so as to define a compositevascular graft.

The method of the present invention also provides for the positioning ofan intermediate structure between the first and second ePTFE tubularstructures. Examples of such structures include an additional ePTFElayer and fibers or thin films of PTFE or other suitable polymers. Thisintermediate structure also contributes to the resultant porosity andstrength of the vascular graft. This intermediate structure can alsopreferably be a resealable polymer layer interposed between the firstand second ePTFE tubular structures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic longitudinal cross-section of a multi-layer ePTFEvascular graft of the present invention.

FIG. 2 is a longitudinal cross-section of an alternate embodiment of thepresent invention producing a multi-layer ePTFE vascular graft.

FIG. 3 is a scanning electron micrograph showing a cross-sectional viewof a vascular graft produced using the present invention.

FIG. 4 is a perspective showing of one of the tubular structures of thegraft of FIG. 1 over-wrapped with a layer of ePTFE tape.

FIG. 5 is a cross-sectional showing of an alternate embodiment of theePTFE vascular graft of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The prosthesis of the preferred embodiments of the present invention isa multi-layered tubular structure which is particularly suited for useas a vascular access graft. The prosthesis is formed of extrudedpolytetrafluoroethylene (PTFE) as PTFE exhibits superiorbiocompatability. In the present invention, a first ePTFE tubularstructure having a first porosity is placed circumferentially interiorto a second ePTFE tubular structure. Further, a resealable polymer layeris interposed as an intermediate structure between said first and secondePTFE tubular structures.

PTFE is particularly suitable for vascular applications as it exhibitslow thrombogenicity. Tubes formed of extruded PTFE may be expanded toform ePTFE tubes where the ePTFE tubes have a fibrous state which isdefined by elongate fibrils interconnected by spaced apart nodes. Suchtubes are said to have a microporous structure, the porosity of which isdetermined by the distance between the surfaces of the nodes, referredto as the intemodal distance (IND). Tubes having a large IND (greaterthan 40 microns) generally exhibit long term patency as the larger porespromote cell endothelization along the inner blood contacting surface.Tubes having lower IND (less than 40 microns) exhibit inferior healingcharacteristics, however they offer superior radial tensile and sutureretention strengths desirable in a vascular graft. The present inventionprovides a composite tubular structure which promotes long term patencyof the graft by providing for enhanced cell endothelization along theinner surface while exhibiting enhanced strength due to the presence ofthe outer layer.

Referring to FIGS. 1 and 2 of the drawings, composite graft 10 of thepresent invention is shown. Graft 10 is an elongate tubular structureformed of PTFE. Graft 10 includes a pair of coaxially disposed ePTFEtubes 12 and 14, tube 12 being the outer tube and tube 14 being theinner tube. A central lumen 15 extends through composite graft 10,defined further by the inner wall 14 a of inner tube 14, which permitsthe passage of blood through graft 10 once the graft is properlyimplanted in the vascular system.

Each tube 12 and 14 may be formed in a separate extrusion process. Theprocess for the paste extrusion of PTFE tubes is well known in theextrusion art. Once extruded, the tubes are expanded to form ePTFE tube.As will be described hereinbelow, the tubes are expanded using differingprocess parameters (rates, deformation levels, temperatures, etc.) todevelop the desired microporous structures. The specifically designedstructure of the resulting composite tube has defined properties ofstrength and porosity which yield a graft 10 having long term patencyand good healing characteristics as well as superior strengthcharacteristics. It is also contemplated within the present invention touse PTFE which was extruded as sheets, expanded, and subsequentlywrapped to form tubes. An ePTFE tape or ribbon helically wrapped into atubular structure is also contemplated within the present invention.

The present invention is designed to produce grafts with substantiallydifferent node/fibril structures with respect to the internal andexternal portions of the graft which are adjacent to the internal andexternal graft surfaces. As an example, the inner tube 14 is designed tohave relatively high IND while the outer tube 12 is designed to have alower IND. Further, a distinct porosity change is clearly defined at theinterface 13 between tubes 12 and 14. The inner tube 14 having a higherIND to allow enhanced cell endothelization, while the outer tube 12having a lower IND provides superior strength to the overall composite.

An electron micrograph of such a structure produced according to thepresent invention is shown in FIG. 3. The disparate IND's between theinner tube 14 and outer tube 12 are clearly evident, along with the stepchange in IND at the interface 13 between the inner tube 14 and outertube 12. In this example, the strength of the interface 13 has beenestablished by the processing conditions described below to fully adherethe inner tube 14 and outer tube together, hence preventing relativemotion and providing enhanced strength.

Graft 10 of the present invention may be formed by expanding a thin wallinner tube 14 at a relatively high degree of elongation, on the order ofapproximately between 400 and 2000% elongation preferably from aboutbetween 700% and 900%. Tube 14 is expanded over a cylindrical mandrel(not shown), such as a stainless steel mandrel at a temperature ofbetween room temperature and 645° F., preferably about 500° F. Tube 14is preferably but not necessarily fully sintered after expansion.Sintering is typically accomplished at a temperature of between 645° F.and 800° F. preferably at about 660° F. and for a time of between about5 minutes to 30 minutes, preferably about 15 minutes. The combination ofthe ePTFE tube 14 over the mandrel is then employed as a second mandrel,over which outer tube 12 is expanded. The ID of the outer tube 12 isselected so that it may be easily but tightly disposed over the OD ofinner tube 14. The composite structure 10 is then sintered at preferablysimilar parameters. The level of elongation of outer tube 12 is lowerthan that of inner tube 14, approximately between 200% and 500%elongation preferably about 400%. The expansion and sintering of outertube 12 over the inner tube 14 serves to adheringly bond the interface13 between the two tubes, resulting in a single composite structure 10.

In an alternate embodiment the outer tube ID may be less than the innertube OD. In this embodiment, the outer tube is thermally or mechanicallyradially dilated to fit over the inner tube. The composite structure maythen be sintered at about 660° F. Construction in this manner provides asnug fit of the tubes, and enhances the bonding interface between tubes,and also may augment recoil properties of an elastomeric intermediatelayer.

As shown in FIG. 3, the resulting composite structure has an innersurface defined by inner tube 14 which exhibits an IND of between 40 and100 microns, spanned by a moderate number of fibrils. Such microporousstructure is sufficiently large so as to promote enhancedcell-endothelization once blood flow is established through graft 10.Such cell-endothelization enhances the long term patency of the graft.

The outer structure, defined by outer tube 12, has a smaller microporousstructure, with IND of about 15-35 microns and a substantial fibrildensity. Such outer structure results in an increase in the strength ofthe outer tube, and hence of the composite structure. Importantly, theouter surface defined by the outer tube 12 exhibits enhanced sutureretention due to the smaller IND.

Furthermore, the resulting composite structure exhibits a sharp porositychange between the outer tube 12 and inner tube 14. This sharp porositytransition is achieved by providing an inner tube 14 having generally agiven uniform porosity therealong and then providing a separate outertube 14 having a resultant different porosity uniformly therealong. Thusa distinct porosity change is exhibited on either side of the interface13 defined between inner tube 14 and outer tube 12.

In addition, the forming process described above results in a bondedinterface between the inner tube 14 and outer tube 12. The interfaceexhibits sufficient interfacial strength resulting from the directsintering of the outer tube 12 over inner tube 14 so as to assurecomplete bonding of the two tubes. The strength of the interface betweenthe two tubes may be independently varied through selection ofprocessing conditions and relative dimensions of precursor extrudedtubes 12 and 14 as desired to yield a range of performance.

Referring now to FIGS. 4 and 5, a further embodiment of the presentinvention is shown. Tubular graft 20 is a composite structure similar tograft 10 described above. Graft 20 includes an outer tube 22 and aninner tube 24 formed generally in the manner described above. In orderto further control the porosity and strength of the graft 20, especiallyat the interface between outer tube 22 and inner tube 24, an additionallayer may be employed in combination with outer tube 22 and inner tube24.

As specifically shown in FIGS. 4 and 5, an additional layer 26 may beemployed between inner tube 24 and outer tube 22. Layer 26 may include ahelical wrap of ePTFE tape 27 placed over inner tube 24. The additionallayer 26, however, may also exist as a sheet, film, yarn, monofilamentor multi filament wrap, or additional tube. The additional layer 26 mayconsist of PTFE, FEP, or other suitable polymer composition to obtainthe desired performance characteristics. Layer 26 may be used to impartenhanced properties of porosity and/or strength to the composite graft20. For example, an additional layer 26 of ePTFE tape 27 having a lowIND and wrapped orthogonally to the length direction of graft 20 wouldincrease the radial strength of the resultant composite graft.Similarly, a layer of ePTFE having a high IND would increase theporosity of the composite structure thereby further promoting cellendothelization and/or tissue ingrowth.

In a preferred embodiment of the present invention, the intermediatelayer may be a resealable polymer layer, employed in order to create aself-sealing graft. The self-sealing graft may be preferably used as avascular access device. The graft is also preferably implantable. Whenused as an access device, the graft allows repeated access to the bloodstream through punctures, which close after removal of the penetratingmember (such as, e.g., a hypodermic needle or cannula) which providedthe access.

The intermediate, or resealable polymer layer may be additionallyaugmented with a pre-sintered PTFE (or FEP) bead wrap, or wire supportcoil. The pre-sintered PTFE bead wrap is a cylindrically extruded solidtube of PTFE that is sintered, then helically wrapped around the desiredlayer (inner, intermediate, or outer). A graft of this embodiment showsenhanced strength and handling characteristics, i.e., crush resistance,kink resistance, etc.

In another preferred embodiment, a self-sustained resealable polymerlayer may be interposed between first and second ePTFE tubularstructures. For the purpose of this specification, the termself-sustained refers to a tubular structure which possesses enoughstructural stability to be formed and subsequently stand alone withoutthe use of additional tubular layers, or any other “molding” typeformation, i.e., not a resinous polymer which is injected, or fills aspace between an outer and inner tube. Some examples include theelastomeric layers employed in the present invention, as well as theresealable intermediate layers shown in Examples 3 and 4 of the presentinvention.

The ePTFE self-sealing graft can be used for any medical technique inwhich repeated hemoaccess is required, for example, but withoutintending to limit the possible applications, intravenous drugadministration, chronic insulin injections, chemotherapy, frequent bloodsamples, connection to artificial lungs, and hyperalimentation. Theself-sealing ePTFE graft is ideally suited for use in chronichemodialysis access, e.g., in a looped forearm graft fistula, straightforearm graft fistula, an axillary graft fistula, or any other AVfistula application. The self-sealing capabilities of the graft arepreferred to provide a graft with greater suture retention, and also toprevent excessive bleeding from a graft after puncture (whether invenous access or otherwise).

The graft is made self-sealing with the use of a resealable polymerlayer interposed between said first and second polymer layer. Theresealable layer functions by primarily two different mechanisms. In oneembodiment, the resealable polymer layer comprises an elastomericcomponent. The term elastomeric as used herein refers to a substancewhich is capable of essentially rebounding to near its initial form orstate after deformation. In another embodiment, the resealable polymerlayer comprises a flowable material layer. The term flowable as usedherein refers to an amorphous material which fills a void created by adeformation or puncture.

It is further contemplated within the present invention to provide acomposite vascular graft with an intermediate resealable layer, andmultiple interior or exterior layers of ePTFE. Furthermore, the use ofmultiple intermediate layers possessing resealable properties is alsocontemplated within the present invention.

A number of different materials may be employed to provide anelastomeric polymer component as contemplated in the present invention.Furthermore, the elastomeric properties of the intermediate layer may beimparted thereto as a result of an inherent property of the materialused, or as a result of the particular method of constructing such alayer. The elastomeric component may also be adhered to the first andsecond ePTFE tubular structures. The adhesion may take place bymechanical means, chemical means (use of an adhesive), either, or both.Some polymers, particularly thermoplastic elastomers, becomesufficiently tacky through heating to adhere to the ePTFE tubularstructures. The elastomeric component may also exert a force in thedirection of the puncture, which if adhered to the first and/or secondePTFE tubular structures may provide for either layer to seal thepuncture site. Some materials which may be used as an elastomericcomponent in various forms include, but are not limited to, polymers andcopolymers, including thermoplastic elastomers and certain silicones,silicone rubbers, synthetic rubbers, polyurethanes, polyethers,polyesters, polyamides and various fluoropolymers, including, but notlimited to PTFE, ePTFE, FEP (fluorinated ethylene propylene copolymer),and PFA (polyfluorinated alkanoate). The materials may be utilized asthe elastomeric polymer layer in a number of different forms which wouldimpart the desired elastomeric characteristics to the layer. In oneembodiment, an extruded polymeric ribbon or tape wrap may be wrappedhelically into a tubular shape under tension. Alternatively, a sheet,fiber, thread, or yarn may also be wrapped under tension to impart anelastomeric layer.

In another preferred embodiment, a polymeric layer may be applied fromsolution. The polymer may be dissolved or partially dissolved in asolvent, and upon evaporation of the solvent, the polymer is depositedas an elastomeric layer. The solvents used in this system must becapable of wetting the ePTFE tubular surfaces. Upon evaporation of thesolvent, an elastomeric layer is deposited which may penetrate into thepores of the adjacent ePTFE layer to provide an anchoring effect for thepolymeric layer. Upon evaporation of the solvent, the elastomeric layermay also shrink to provide the desired elastomeric characteristics.

In another embodiment of the elastomeric layer of the present invention,a solvent spun polyurethane as disclosed in U.S. Pat. Nos. 4,810,749;4,738,740; 4,743,252 and 5,229,431, herein incorporated by reference,may be employed. From such elastomeric fibers may be formed a woven ornon-woven textile-like layer with sufficient fiber density to form asealing layer while allowing a puncturing member such as a hypodermicneedle or cannula to penetrate between the individual fibers.Furthermore, the elastomeric fibers of said textile-like structure maybe employed under tension or compression to facilitate the recovery ofthe fibers displaced by the penetrating member to their originalposition after removal by the penetrating member.

Furthermore the elastomeric layer of the present invention mayadditionally be impregnated with a gel to provide enhanced sealingcapabilities. Examples of such gels are hydrogels formed from naturalmaterials including, but not limited to, gelatin, collagen, albumin,casein, algin, carboxy methyl cellulose, carageenan, furcellaran,agarose, guar, locust bean gum, gum arabic, hydroxyethyl cellulose,hydroxypropyl cellulose, methyl cellulose, hydroxyalkylmethyl cellulose,pectin, partially deacetylated chitosan, starch and starch derivatives,including amylose and amylopectin, xanthan, polylysine, hyaluronic acid,and its derivatives, heparin, their salts, and mixtures thereof.

A number of different flowable polymer layers may be interposed betweensaid first and second tubular structures to provide a self-sealinggraft. The flowable polymer layer seals the graft by possessing anamorphous quality which fills in any space left open subsequent topuncture of the graft. It may simply fill in the space left open in theinterposed middle layer, or it may additionally penetrate into the firstand/or second ePTFE tubular structures to fill any void left formpuncture of either layer.

An example of a flowable polymer which may be used in the presentinvention is an uncured or partially cured polymer. The polymer may becured by a number of activating means which would activate curingsubsequent to puncture of the graft, thereby sealing with the curing ofthe polymer. Examples of materials for such a flowable layer include,but are not limited to, uncured elastomers such as natural or syntheticrubbers, and natural gums such as gum arabic. Materials that areparticularly useful in a flowable layer include non-crosslinkedpolyisobutylene which is also known as uncured butyl rubber.

Another flowable polymer layer which may be employed in the presentinvention a gel. Gels are generally suspensions or emulsions of polymerswhich have properties intermediate the liquid and solid states. Ahydrogel may also be used in the present invention, and refers topolymeric material which swells in water without dissolving, and whichretains a significant amount of water in its structure. The gels andhydrogels employed in the present invention may be biodegradable, ornon-biodegradable. They also further may have polymeric beads (not to beconfused with the pre-sintered PTFE bead-wrap, which imparts structuralstability) suspended within the gel to effectuate sealing of theprosthesis. Some examples of gels which may be used in the presentinvention include, but are not limited to, silicone gels, gum arabic,and low molecular weight ethylene/vinyl acetate polymers.

The following examples serve to provide further appreciation of theinvention but are not meant in any way to restrict the scope of theinvention.

EXAMPLE I

A thin extruded tube having wall thickness of 0.41 mm and an innerdiameter of 6.2 mm was expanded over a stainless steel mandrel at 500°F. to 900% elongation. The ePTFE tube was then sintered at 660° F. for14 minutes, cooled, and removed from the oven. A second thin extrudedtube having wall thickness of 0.45 mm and an inner diameter of 6.9 mmwas expanded over the first tube/mandrel combination at 500° F. and 400%elongation. The composite was then sintered at 660° F. for 14 minutes,cooled and removed from the oven. The resultant composite tube had awall thickness of 0.65 mm and ID of 5.8 mm.

EXAMPLE 2

A thin extruded tube having wall thickness of 0.41 mm and an innerdiameter of 6.2 mm was expanded over a stainless steel mandrel at 500°F. to 700% elongation. The ePTFE tube was then sintered at 660° F. for14 minutes, cooled, and removed from the oven. A second thin extrudedtube having wall thickness of 0.45 mm and an inner diameter of 6.9 mmwas expanded over the first tube at 500° F. and 400% elongation. Thecomposite was sintered at 660° F. for 14 minutes, cooled, and removedfrom the oven. The resultant composite tube had a wall thickness of 0.67mm and an inner diameter of 5.8 mm.

Table I presents physical property data for a vascular graft of the typedepicted in Example I described above. The composite graft was removedfrom the mandrel and subjected to standard testing of radial tensilestrength and suture hole elongation. The radial strength of the900%/400% composite graft is equivalent to a single layer 400%elongation graft and substantially stronger than a single layer 900%elongation graft, despite an overall thinner wall dimension.Additionally, the superior strength of the composite graft isdemonstrated by the higher elongation capable of being borne by thegraft prior to failure. The lower suture hole elongation, indicative ofa smaller tear being caused by suturing and tensioning at a fixed valueof 100 grams is clearly demonstrated for the graft prepared by themethod of the current invention. TABLE 1 400% 900%/ Elongation 400% 900%Single Elongation Elongation Physical Property Layer Composite SingleLayer Measurement Graft Graft Graft Radial Tensile Strength (kg/mm²)0.48 0.48 0.2 Radial Strain at Break (%) 550 690 531 Suture HoleElongation (%) 87 81 158 Wall Thickness 0.72 0.65 0.73

EXAMPLE 3

Three composite grafts were constructed and their ability to resealafter a puncture was tested. Graft No. 1 is an ePTFE helicallytape-wrapped graft with no resealable layer, and graft Nos. two (2) andthree (3) were constructed with a resealable intermediate layer in thebelow-described procedure.

Graft No. 1 is an ePTFE graft used as the control in the followingexperiment. Graft 2 was constructed by first placing an ePTFE tubularstructure with an inner diameter of 5 millimeters on a mandrel. Athermoplastic elastomer tubing was then slid over the ePTFE tube.Because of the tackiness of the thermoplastic elastomeric tubing, it wasnecessary to manipulate the tubing by rolling and stretching it in orderto maneuver it over the first ePTFE tubular structure to lie evenlythereon. A second ePTFE tubular structure with an inner diameter of five(5) millimeters was then radially stretched, or expanded to yield anePTFE tubular structure with an inner diameter of 8 millimeters. A metalsleeve was then placed over the thermoplastic elastomer-covered tubularstructure. The second 8 mm inner diameter ePTFE tubular structure wasthen placed onto the metal sleeve. The metal sleeve was then retractedallowing the second tubular structure to come into contact with thethermoplastic elastomer.

Both grafts Nos. 2 and 3 were prepared using this procedure. Graft 2 wasthen placed in an oven and heated at 350° F. for 10 minutes. Thereappeared to be little bonding between the layers, and the graft was thenheated for an additional 10 minutes at 450° F.

Graft 3 was heated for five minutes at 400° F. The material did notappear to bond together, so the graft was then heated at 425° F. for anadditional five minutes.

Grafts Nos. 1-3 were then tested for quality control. Each graft wasplaced in a water entry pressure measuring device to provide a constantpressure of water within the graft. The water pressure was maintained atthree pounds per square inch. The grafts were then punctured with a 20gauge needle. The needle was then removed and any water leaving thepuncture site was collected in a beaker and measured over the time ofcollection. This procedure was followed for a number of test runs. Theresults are shown in table two below. TABLE 2 Graft No. 1 Graft No. 2Graft No. 3 Run (grams water/30 (grams water/30 (grams water/30 Numberseconds) seconds) seconds) 1 21.7 0.2 1.2 2 20.0 1.3 0.5 3 23.1 0.2 — 420.0 1.4 — 5 21.9 — — Average Of 21.34 0.775 0.85 Trial Runs

Graft No. 1 leaked steadily, as the puncture did not reseal. While graftnumbers 2 and 3 showed minimal leakage. In both cases, the water leakedin a small trickle in the first few seconds (2-5 seconds), then stoppedor slowed to an immeasurable seepage.

EXAMPLE 4

Three additional grafts were constructed with an intermediate resealablelayer and tested to determine their ability to seal after puncture.

Graft No.4 was made using an ePTFE graft with an initial 5 millimeterinner diameter as the inner tubular structure. The 5 mm ePTFE tube wasextruded using a die insert of 0.257 inches, and a mandrel of 0.226inches. The inner tube was then stretched longitudinally to 500% itsoriginal length, and sintered. The inner tube was then stretchedradially by placing it on a 5.95 mm mandrel. A pre-sintered PTFEbead-wrap (0.014 inch ±0.002 inch diameter, length approximately 30 cm)was then helically wrapped around the exterior of the inner tube at 650revolutions per minute (RPM), and with a mandrel speed traversely at 800RPMs. The wrap helically repeated on the tube at approximately every 3.5cm, and at an angle of approximately 10°-50° with respect to a radialaxis. After wrapping, the coil wrapped tube was then heated in an ovenat 663° F. for 10 minutes to sinter the beads to the grafts.

A second ePTFE tube was then added exterior the beaded coil and innertube. The second ePTFE tube also had a 5 millimeter inner diameter, andwas a tube extruded using a die insert of 0.271 inches and mandrel size0.257 inches, and was stretched to longitudinally 500% its originallength and sintered. The second ePTFE tube was then radially stretchedover a tapered 6-10 mm mandrel to a graft of inner diameter of 10 mms.The second graft was then transferred to a 10 mm hollow mandrel withinwhich the inner bead-wrapped graft was placed. The hollow mandrel wasthen slid out to leave the second ePTFE tube exteriorly placed on thebead covered graft. The composite device was then placed in an oven for20 minutes and heated at 663° F. Three 3 cm long tubular rings ofthermoplastic elastomer (C-FLEX®) were then placed over the compositestent graft. The rings had an inner diameter of 6.5 mms. A third outerePTFE tubular structure was then placed over the C-FLEX rings. The thirdouter tubular structure was a 3 mm inner diameter ePTFE extruded tubewas made using a die insert of 0.189 inches, and was stretchedlongitudinally to 700% its original length and sintered. The third outerstructure was then expanded radially by stretching the tube over a 4-7mm continuously tapered mandrel, then further radially expanded over a6-10 mm continuously tapered mandrel. It was then placed on a 10 mmhollow mandrel with the C-FLEX covered composite graft placed within themandrel, and the outer tube then covers the C-FLEX® upon removal of thehollow mandrel. Graft 4 was then heated for 5 minutes at 435° F.

Graft No. 5 was constructed using a 5 mm inner diameter ePTFE extrudedtube as the inner tubular structure. The 5 mm tube was then radiallystretched over a 5.95 mm diameter mandrel. A corethane intermediatelayer was then spun into a tube of 6 mm diameter with 250 passes, andsubsequently loaded onto the inner ePTFE tube. A second outer ePTFEtubular structure (originally a 5 mm inner diameter) was then stretchedto 10 mm over a 6-10 mm continuously tapered mandrel. Graft No. 5 wasthen heated for 15 minutes at 400° F.

Graft No. 6 was made using a 5 mm inner diameter ePTFE graft as theinner tubular structure. The inner tube was then stretched over a 6.2 mmhollow expansion mandrel. An ePTFE yarn was then wrapped in two helicaldirections over the inner tube. A corethane layer was then spun over theyarn wrapping as the third tubular layer at a mandrel speed of 1,000RPMs and a wrap angle of 50 degrees. The corethane covered graft wasthen heated at 230° F. for 10 minutes. An outer ePTFE tube with a 5 mminner diameter was then stretched to 10 mm over a 6-10 mm continuouslytapered mandrel. It was then mounted on the corethane layer with the useof the hollow mandrel. Graft 6 was then heated for 30 minutes at 340° F.

Grafts 4-6 were all tested by puncturing them with a constant pressurewater source attached to them as done with Grafts Nos. 1-3. The resultsare shown in Table 3 below. TABLE 3 Graft 5 Graft 6 Graft 4 (grams(grams water/ Run No. (grams water/seconds) water/seconds) seconds) 10.2 0 0 2 0 0 0 3 0 0.7 0

Various changes to the foregoing described and shown structures wouldnow be evident to those skilled in the art. Accordingly, theparticularly disclosed scope of the invention is set forth in thefollowing claims.

1. A multi-layered ePTFE graft comprising: a first ePTFE tubularstructure having a first internodal distance; a second ePTFE tubularstructure having a second internodal distance different than said firstintemodal distance, said second ePTFE tubular structure being disposedabout said first ePTFE tubular structure; and a self-sealing gelinterposed between said first and second ePTFE tubular structures,wherein said gel is selected from the group consisting of gelatin,collagen, albumin, casein, algin, carboxymethyl cellulose, carageenan,furcellan, agarose, guar, locus bean gum, gum arabic, hydroxyethylcellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyalkylmethylcellulose, pectin, partially deacetylated chitosan, starch and starchderivatives, including amylase and amylopectin, xanthan, polylysine,hyaluronic acid, and its derivatives, heparin, their salts, and mixturesthereof.
 2. A multi-layered graft according to claim 1, wherein saidfirst intemodal distance is greater than said second internodaldistance.
 3. A multi-layered graft according to claim 1, wherein saidsecond ePTFE tubular structure is disposed externally about said firstePTFE tubular structure.
 4. A multi-layered graft according to claim 1,wherein said self-sealing gel comprises a single layer having resealableproperties.
 5. A multi-layered graft according to claim 1, wherein saidself-sealing gel is flowable.
 6. A multi-layered ePTFE vascular graftuseful for repeated hemoaccess comprising: a first ePTFE tubularstructure having a first internodal distance; a second ePTFE tubularstructure having a second internodal distance different than said firstinternodal distance, said second ePTFE tubular structure being disposedabout said first ePTFE tubular structure; and a self-sealing gelinterposed between said first and second ePTFE tubular structures,wherein said gel is selected from the group consisting of gelatin,collagen, albumin, casein, algin, carboxymethyl cellulose, carageenan,furcellan, agarose, guar, locus bean gum, gum arabic, hydroxyethylcellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyalkylmethylcellulose, pectin, partially deacetylated chitosan, starch and starchderivatives, including amylase and amylopectin, xanthan, polylysine,hyaluronic acid, and its derivatives, heparin, their salts, and mixturesthereof.
 7. A multi-layered graft according to claim 6, wherein saidfirst internodal distance is greater than said second internodaldistance.
 8. A multi-layered graft according to claim 6, wherein saidsecond ePTFE tubular structure is disposed externally about said firstePTFE tubular structure.
 9. A multi-layered graft according to claim 6,wherein said self-sealing gel comprises a single layer having resealableproperties.
 10. A multi-layered ePTFE graft comprising: a first ePTFEtubular structure having a first internodal distance; a second ePTFEtubular structure having a second internodal distance different thansaid first internodal distance, said second ePTFE tubular structurebeing disposed about said first ePTFE tubular structure; and abiodegradable material interposed between said first and second ePTFEtubular structures.
 11. A multi-layered graft according to claim 10,wherein the biodegradable material is a gel.
 12. A multi-layered ePTFEgraft comprising: a first ePTFE tubular structure; and a second ePTFEtubular structure, said second ePTFE tubular structure being disposedabout said first ePTFE tubular structure; wherein the graft exhibits aradial tensile strength of at least 0.48 kg/mm².
 13. The multi-layeredgraft of claim 12, wherein said first ePTFE tubular structure has afirst porosity and said second ePTFE tubular structure has a secondporosity.
 14. The multi-layered graft of claim 13, wherein said secondporosity is different than sand first porosity.
 15. A multi-layeredePTFE graft comprising: a first ePTFE tubular structure; and a secondePTFE tubular structure, said second ePTFE tubular structure beingdisposed about said first ePTFE tubular structure; wherein the graft iscapable of withstanding elongation of at least 690% without breaking.16. The multi-layered graft of claim 15, wherein said first ePTFEtubular structure has a first porosity and said second ePTFE structurehas a second porosity.
 17. The multi-layered graft of claim 16, whereinsaid second porosity is different than said first porosity.
 18. Amulti-layered ePTFE graft comprising: a first ePTFE tubular structure;and a second ePTFE tubular structure, said second ePTFE tubularstructure being disposed about said first ePTFE tubular structure; and aself-sealing material interposed between said first and second ePTFEtubular structures, wherein the graft exhibits no or immeasurableleakage 30 seconds subsequent to puncture with a water source.
 19. Themulti-layered graft of claim 18, wherein said first ePTFE tubularstructure has a first porosity and said second ePTFE tubular structurehas a second porosity.
 20. The multi-layered graft of claim 19, whereinsaid second porosity is different than said first porosity.